Axerion seeks to develop therapeutic agents to promote the recovery of neurological function through axonal fiber growth and enhanced plasticity after brain or spinal cord damage. In nearly all neurological conditions, a substantial portion of brain and spinal cord is preserved. If remaining healthy tissue can be "rewired" with appropriate axonal connections, improved neurological function can result. Without treatment, axonal growth is extremely limited in the adult brain and spinal cord, and recovery is typically restricted. Today, no FDA-approved therapeutic promotes new connections between surviving nerve cells. It has been known for a number of years that the white matter or myelin of the central nervous system inhibits axon growth in the adult brain and spinal cord. A molecular characterization of inhibitors in myelin led to our identification of the protein, Nogo. We also identified a Receptor protein for Nogo (NgR1). Molecules with Nogo/NogoReceptor blocking activity promote the growth of axons in the adult spinal cord and promote recovery of walking performance in injured animals without side-effects. We have demonstrated benefit in both acute and chronic spinal contusion models with Axerion's NgR(310)ecto-Fc protein therapy. Functional recovery of rats after stroke is also enhanced by this treatment. Our objective in this Project is to develop NogoReceptor protein therapy for the recovery of function by local intrathecal administration in chronic spinal cord injury. Specifically, Axerion will achieve an Investigational New Drug (IND) filing with the Food and Drug Administration (FDA) so that clinical trials of Axerion's NgR(310)ecto-Fc protein can be initiated. The proposed work is essential to move this promising therapy across the so-called "Valley of Death" in commercialization, from academic discovery studies to proof-of-concept clinical trials. We will accomplish this goal in 5 steps: NgR Good Manufacturing Practice (GMP) Manufacture, Good Laboratory Practice (GLP) Assay Development for NgR, Large Animal Pharmacodynamics of NgR(310)ecto-Fc, Toxicology Studies of NgR(310)ecto-Fc, and IND Filing. Support for these 5 steps will ensure that commercialization and clinical testing of a novel axonal growth therapy for neurologic recovery from spinal cord injury and stroke occurs. PUBLIC HEALTH RELEVANCE: Axerion aims to commercialize therapeutic agents to promote the recovery of neurological function through axonal fiber growth and enhanced plasticity after spinal cord injury or stroke. The NgR(310)ecto-Fc protein blocks the action of myelin inhibitors and allows axonal growth and functional recovery in rodent models. The current project will develop the GMP/GLP methods and examine toxicology to allow Investigational New Drug (IND) filing with the Food and Drug Administration (FDA) so that clinical trials of Axerion's NgR(310)ecto-Fc protein can be initiated.